Many active pharmaceutical compounds may only be beneficially employed within very specific dosage ranges, with ineffective or even deleterious effects being encountered if too high or too low a dosage is employed. Accordingly, it is necessary that such compounds be formulated in a uniform manner such that a consistent dosage of such active compound can be readily manufactured and administered.
Particular problems exist with respect to the formulation of actives which are in the form of fine powders. These actives are typically blended with excipients employing wet granulation techniques wherein such ingredients are utilized in the form of a wet paste. The paste is blended with the pharmaceutically active powder, then dried, ground and tableted. However, such wet granulation processes are disfavored by the pharmaceutical industry because they are labor intensive, require special equipment and are highly susceptible to contamination. Moreover, it is especially difficult to employ these wet techniques for the formulation of actives, such as phenylpropanolamine and the like, which have a low bulk density and tend to be difficult to uniformly disperse in the wet granulation.
While it would be more economical to dry blend the active particulate material with powdered excipient and directly form tablets therefrom, the low levels of the particulate incorporated and the fine particle size thereof makes uniform blending exceptionally difficult. Specifically, because of such factors, separation of the active particulate from the excipient mass can occur during the granulation, blending and/or tableting process with the result that the manufactured products do not meet uniform assay requirements.
In order to minimize the segregation problem, pharmaceutical manufacturers have tried increasing the particle size of active materials by encapsulating such actives in gelatin or other film formers in addition to fats as well as by pregranulating the active with an excipient prior to formulating and tableting. However, neither encapsulation nor pregranulation may effectively prevent segregation as in many instances separation may occur upon the grinding or milling of such encapsulates or pregranulates. Moreover, these processes increase the number of formulating steps required and thus involve the incurring of additional expense.
Thus, it would be desirable to possess a pharmaceutical composition which contains a uniform concentration of particulate active material, which composition can be easily and inexpensively manufactured with low risk of contamination.
Accordingly, it is an object of this invention to provide a pharmaceutical composition having a uniform dispersion of particulate active material.
It is a further object of this invention to provide a process for economically preparing a pharmaceutical composition having a uniform dispersion of particulate active material.
The above objects and other additional objects will become more fully apparent from the following description and accompanying Examples.